Valproic acid induces three novel cytotoxic secondary metabolites in Diaporthe sp., an endophytic fungus from Datura inoxia Mill

Bioorg Med Chem Lett. 2018 Jul 1;28(12):2217-2221. doi: 10.1016/j.bmcl.2018.04.018. Epub 2018 Apr 10.

Abstract

Addition of the valproic acid (histone deacetylases inhibitor) to a culture of an endophytic fungus Diaporthe sp. harbored from Datura inoxia significantly altered its secondary metabolic profile and resulted in the isolation of three novel compounds, identified as xylarolide A (1), diportharine A (2) and xylarolide B (3) along with one known compound xylarolide (4). The structures of all the compounds (1-4) were determined by detailed analysis of 1D and 2D NMR spectroscopic data. The relative configurations of compounds 1-3 were determined with the help of NOESY data and comparison of optical rotations with similar compounds with established stereochemistry. All the isolated compounds were screened for antibacterial, antioxidant and cytotoxic activities. Xylarolide A (1) and xylarolide (4) displayed significant growth inhibition of MIAPaCa-2 with an IC50 of 20 and 32 µM respectively and against PC-3 with an IC50 of 14 and 18 µM respectively. Moreover, compound 1 displayed significant DPPH scavenging activity with EC50 of 10.3 µM using ascorbic acid as a positive control.

Keywords: Anti-oxidant activity; Cytotoxic activity; Datura inoxia; Diaporthe sp.; Endophytic fungi; MIA-Pa-Ca-2-cells; Xylarolide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Ascomycota / chemistry*
  • Ascomycota / growth & development
  • Ascomycota / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Datura / chemistry
  • Datura / microbiology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Escherichia coli / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology*
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Valproic Acid / chemistry
  • Valproic Acid / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Peptides, Cyclic
  • xylarotide A
  • xylarotide B
  • Valproic Acid